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CLINICAL RESEARCH: ATHEROSCLEROSIS

Is Plasma Oxidized Low-Density Lipoprotein, Measured With the Widely Used Antibody 4E6, an Independent Predictor of Coronary Heart Disease Among U.S. Men and Women?

Tianying Wu, MD, PhD^_*,_*, Walter C. Willett, MD, DrPh^_*,,, Nader Rifai, PhD^||, Iris Shai, PhD^_*, JoAnn E. Manson, MD, DrPh^,, and Eric B. Rimm, ScD^_*,,

^_* Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
Channing Laboratory, Harvard Medical School and Brigham & Women’s Hospital, Boston, Massachusetts
Division of Preventive Medicine, Department of Medicine, Harvard Medical School and Brigham & Women’s Hospital, Boston, Massachusetts
^|| Department of Laboratory Medicine, Children’s Hospital and Harvard Medical School, Boston, Massachusetts

Manuscript received January 6, 2006; revised manuscript received March 17, 2006, accepted March 20, 2006.

^_* Reprint requests and correspondence: Dr. Tianying Wu, Department of Nutrition, Harvard School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115. (Email: tianying{at}hsph.harvard.edu).

OBJECTIVES: Our aim was to examine whether circulating oxidized low-density lipoprotein (oxLDL) is a predictor of coronary heart disease (CHD) independent of lipid markers and to compare oxLDL, apolipoprotein B100 (apoB), and total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio as predictors of CHD.

BACKGROUND: Measurement of circulating oxLDL with antibody 4E6, has been widely used in many studies; however, few large prospective studies have examined whether this marker is a predictor of CHD independent of lipids and compared oxLDL with other important lipid predictors.

METHODS: After 6 years of follow-up among 18,140 men from the HPFS (Health Professionals Follow-up Study) and 8 years among 32,826 women from the Nurses’ Health Study who provided blood samples at baseline, we identified incident nonfatal myocardial infarction or fatal CHD in 266 men and 235 women. Each case was matched with two control subjects by age, smoking, and time of blood draw. The oxLDL was measured via enzyme-linked immunosorbent assay with antibody 4E6 against oxidized apoB.

RESULTS: Among both men and women, oxLDL was significantly related to risk of CHD in multivariate analysis before adjustment for any lipid markers. However, when oxLDL, LDL cholesterol, HDL-C, and triglycerides were mutually adjusted, oxLDL was no longer predictive. When oxLDL and apoB were mutually adjusted, only apoB was predictive of CHD. Similar results were found when oxLDL and TC/HDL-C ratio were mutually adjusted.

CONCLUSIONS: Our results suggest that circulating oxLDL, measured with antibody 4E6, is not an independent overall predictor of CHD after adjustment of lipid markers and is less predictive in development of CHD than apoB and TC/HDL-C ratio.

Abbreviations and Acronyms   ApoB = apolipoprotein B100   CHD = coronary heart disease   CI = confidence interval   ELISA = enzyme-linked immunosorbent assay   HDL-C = high-density lipoprotein-cholesterol   LRT = likelihood ratio test   MI = myocardial infarction   oxLDL = oxidized low-density lipoprotein   OR = odds ratio   RR = relative risk   TC = total cholesterol

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